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. 2004 Jan;166(1):611–619. doi: 10.1534/genetics.166.1.611

Controlling the proportion of false positives in multiple dependent tests.

R L Fernando 1, D Nettleton 1, B R Southey 1, J C M Dekkers 1, M F Rothschild 1, M Soller 1
PMCID: PMC1470704  PMID: 15020448

Abstract

Genome scan mapping experiments involve multiple tests of significance. Thus, controlling the error rate in such experiments is important. Simple extension of classical concepts results in attempts to control the genomewise error rate (GWER), i.e., the probability of even a single false positive among all tests. This results in very stringent comparisonwise error rates (CWER) and, consequently, low experimental power. We here present an approach based on controlling the proportion of false positives (PFP) among all positive test results. The CWER needed to attain a desired PFP level does not depend on the correlation among the tests or on the number of tests as in other approaches. To estimate the PFP it is necessary to estimate the proportion of true null hypotheses. Here we show how this can be estimated directly from experimental results. The PFP approach is similar to the false discovery rate (FDR) and positive false discovery rate (pFDR) approaches. For a fixed CWER, we have estimated PFP, FDR, pFDR, and GWER through simulation under a variety of models to illustrate practical and philosophical similarities and differences among the methods.

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Selected References

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  1. Elston R. C. 1996 William Allan Award Address. Algorithms and inferences: the challenge of multifactorial diseases. Am J Hum Genet. 1997 Feb;60(2):255–262. [PMC free article] [PubMed] [Google Scholar]
  2. Elston R. C., Lange K. The prior probability of autosomal linkage. Ann Hum Genet. 1975 Jan;38(3):341–350. doi: 10.1111/j.1469-1809.1975.tb00619.x. [DOI] [PubMed] [Google Scholar]
  3. Lander E., Kruglyak L. Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results. Nat Genet. 1995 Nov;11(3):241–247. doi: 10.1038/ng1195-241. [DOI] [PubMed] [Google Scholar]
  4. MORTON N. E. Sequential tests for the detection of linkage. Am J Hum Genet. 1955 Sep;7(3):277–318. [PMC free article] [PubMed] [Google Scholar]
  5. Mosig M. O., Lipkin E., Khutoreskaya G., Tchourzyna E., Soller M., Friedmann A. A whole genome scan for quantitative trait loci affecting milk protein percentage in Israeli-Holstein cattle, by means of selective milk DNA pooling in a daughter design, using an adjusted false discovery rate criterion. Genetics. 2001 Apr;157(4):1683–1698. doi: 10.1093/genetics/157.4.1683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Risch N. A note on multiple testing procedures in linkage analysis. Am J Hum Genet. 1991 Jun;48(6):1058–1064. [PMC free article] [PubMed] [Google Scholar]

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